1. Field of the Invention
This invention relates to blood serum separator tubes useful for separating the serum and red blood cell portions of a collected blood sample through centrifugation. More specifically, the invention relates to arrangements for improving the performance of thixotropic gels used as partitioning materials in such serum separator tubes. 2. Brief Description of the Prior Art
Blood collection and separating devices are known in which a collected sample of blood is added to a glass tube containing a thixotropic gel having a density between that of blood serum and red blood cells. During centrifugation, the thixotropic gel acts as a partitioning material and is displaced upwardly in the blood sample until it reaches an equilibrium point located between the blood serum or plasma and the heavier red cell portions of the blood. At equilibrium, the gel forms a chemical and mechanical barrier between the serum and the heavier coagulum. The lighter fraction can then be easily decanted directly from the upper portion of the collection tube for analysis in automated blood analyzing equipment.
FIG. 1 shows a prior art blood serum separator tube 10 including a tube 12 which may be silicone-coated glass, a stopper 14 which may be silicone-lubricated butyl rubber, and a partitioning material or gel 16 which is an inert, thixotropic material. Such apparatus is described in Gigliello, et al., U.S. Pat. No. 3,920,549 for "Method and Apparatus for Multiphase Fluid Collection and Separation," that entire disclosure hereby being incorporated by reference.
In the prior art configuration illustrated in FIG. 1, the apparatus further includes a smaller moveable cup or energizer 18 positioned inside the tube 12 and on top of the thixotropic gel 16. Furthermore, the energizer 18, which is open at its upper end 19, may contain microscopic glass particles 20 which serve to promote coagulation by providing an expanded surface area inside the tube 12 during centrifugation. In this blood serum separator tube 10, the thixotropic gel 16 is exposed to any atmosphere 22 contained in the tube 10 at an annular surface 25 around the gel energizer 18, between the energizer 18 and the inner wall 13 of the tube.
In common use, blood is drawn into the tube 12, and the glass powder 20 is suspended throughout the collected blood. Coagulation occurs for a predetermined period of time, e.g., 15 minutes, and then the tube is centrifuged for a predetermined length of time at a particular centrifugation speed, the particular speed depending upon the size of the centrifuge being used. During centrifugation, the coagulum fills the energizer 18 and drives the energizer 18 into the gel 16 at the base 15 of the tube 12, causing the gel 16 to temporarily change viscosity. The gel 16 then flows up around the sides of the energizer 18 towards a mid-portion 17 of the tube until it reaches an equilibrium point between the separated serum and coagulum. Also moving below the gel barrier with the coagulum are the glass powder particles 20.
The specific gravity of blood serum ranges from between about 1.026 and 1.031, and the specific gravity of the coagulum or clot portion ranges from between about 1.092 and 1.095. Once centrifugation is complete, the lighter serum fraction may be easily removed for further analysis, for example, in automated blood-analyzing apparatus.
A preferred thixotropic composition for use in such separator tubes is described in the inventor's own prior U.S. Pat. No. 4,386,003, for "Blood Separating Composition," the entire disclosure of which is hereby incorporated by reference. As described therein, a preferred thixotropic gel material is a silica-silicone fluid gel formed by the reaction between silicone fluid, a filler material (such as silica particles) and a thixotropic property-imparting amount of a network former. The relative amounts of the gel components are selected so as to yield a gel having a specific gravity ranging between about 1.03 and 1.09, and preferably about 1.04. Silicone fluids used to prepare such gels are conventionally characterized as "silicone oils," and the terms "silicone fluid" and "silicone oil" as used herein are interchangeable.
While silica-silicone fluid gels provide a superior chemical and physical barrier in blood serum separator tubes as described above, a known problem in the use of such gels is that oil-like films or droplets of pure silicone oil separate from the gel material at exposed surfaces of the gel material during storage. This problem is noted in Murty, U.S. Pat. 4,180,465 for "Fluid Collection Device With Phase Separation Means." Such exposed surfaces occur at the annular surface 25 between the gel energizer 18 and inner wall 13 of the tube 12. Also, bubbles formed in the gel during manufacture present the same atmospheric contact and thus also contribute to separation of silicone oils from the gel during storage. Still further, when a separator tube as shown in FIG. 1 is stored on its side, the energizer 18 may move toward or against the inner wall 13 of the tube 12 by the influence of gravity. In so moving, a capillary effect may further promote separation of silicone oil from the thixotropic gel 16.
The silicone oils are lighter in density than the formed gel barrier and therefore rise into or on top of the separated serum portion of the blood sample, toward the stopper 14. Upon being decanted along with the blood serum, such silicone oils cause clogging and fouling of automated blood analyzing apparatus.
The problem of oil separation is not unique to silicone-based thixotropic gels. The same degradation has been found to occur in many hydrocarbon-based gel compositions. Such hydrocarbon-based gels include polyester, disclosed in Kessler et al., U.S. Pat. No. 4,350,593, for "Assembly, Compositions and Method for Separating Blood"; copolyesters, disclosed in Lamont et al., U.S. Pat. No. 4,101,422, for "Copolyesters Useful In Blood Separation Assemblies", and also in Lamont et al., U.S. Pat. No. 4,148,764, for "Copolyesters Useful In Blood Separation Assemblies"; polybutene, disclosed in Zine, Jr., U.S. Pat. No. 4,021,340, for "Blood Separating Composition"; polybutadiene, disclosed in Semersky, U.S. Pat. No. 4,235,725, for "Sterile Blood-Collecting and Separating Device"; and alpha-olefin-dimaleate copolymer, disclosed in Ichikawa et al., U.S. Pat. No. 4,426,290, for "Apparatus for Separating Blood." Cornell, U.S. Pat. No. 4,055,501, for "Fluid Collection Device With Phase Partitioning Means," also discloses hydrocarbon-based materials including polybutene and polybutadiene. The entire disclosure of each of these U.S. patents is hereby expressly incorporated by reference.
In Ayres, U.S. Pat. No. 3,909,419 for "Plasma Separator With Squeezed Sealant," a blood collection and separator assembly is described, including a pair of cylinders slidably disposed in the tube. The top cylinder has a specific gravity greater than the bottom cylinder so that upon centrifugation, the cylinders will move together. Upon such movement, the cylinders rupture and squeeze out one or more layers of microencapsulated beads of gelatin or other sealant disposed therebetween. Positioning of the seal is established by selecting the average specific gravity of the top and bottom cylinders to be between that of the plasma and coagulum. The microencapsulated sealant thereby forms a seal between the cylinders and the inner wall of the tube slightly above the interface between the two phases of the blood. Proper positioning of the described seal depends on accurate mechanical operation of the dual cylinder arrangement.
Thus, the need for an improved blood serum separating tube having the benefits but not the drawbacks of the various gel materials is readily seen.